Glofitamab plus gemcitabine and oxaliplatin shows survival benefit in R/R DLBCL

Results from the phase III STARGLO trial demonstrated a statistically significant and clinically meaningful improvement in overall survival with glofitamab in combination with gemcitabine and oxaliplatin (Glofit-GemOx) versus rituximab in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy.

Glofitamab is an off-the-shelf, fixed-duration treatment for relapsed/refractory large B-cell lymphoma (R/R LBCL). Phase I/II pivotal trial experience in patients with R/R diffuse large B-cell lymphoma (DLBCL) after at least two prior therapies demonstrated high rates of complete response (CR), with the majority lasting for more than two years. At EHA 2024, efficacy and safety results of glofitamab in combination with gemcitabine and oxaliplatin (Glofit-GemOx) versus rituximab plus gemcitabine and oxaliplatin (R-GemOx) in patients with R/R DLBCL after at least one prior line of therapy from the global, randomised, phase III STARGLO trial were presented.

Study design

The phase III STARGLO trial enrolled patients with R/R DLBCL after at least one prior systemic therapy. Patients with one prior line must be transplant-ineligible (based on age ≥70 years, organ dysfunction, ECOG performance status ≥2, patient refusal for ASCT, or other investigator-assessed comorbidities). All patients had an ECOG performance status 0-2 and were randomised in a 2:1 ratio to eight 21-day cycles of Glofit-GemOx (step-up dosing in cycle 1, 30 mg administered on Day 1 from cycle 2 onwards) or R-GemOx (administered on Day 1 of each cycle). Patients in the Glofit-GemOx arm could receive glofitamab 30 mg administered on day 1 of each cycle for cycles 9-12. Primary endpoint of the study was overall survival (OS) and hierarchical secondary endpoints were progression-free survival (PFS), complete response rate and duration of complete response by independent review committee (IRC) assessment.

Results

Out of the 274 patients that were enrolled, 62.8% received one prior line of therapy and 37.2% of patients were enrolled after at least two prior lines. Overall, 55.8% had primary refractory disease and 60.6% were refractory to last therapy. After a median follow-up of 20.7 months, median OS was 12.9 months for R-GemOx and 25.5 months for Glofit-GemOx, resulting in a 38% reduction in the risk of death (HR[95%CI]: 0.62[0.43-0.88], p= 0.006). The two-year OS rates were respectively 33.5% and 52.8%. At a median follow-up of 16.1 months, median PFS was reported at 3.6 months for R-GemOx but was 13.8 months for Glofit-GemOx, translating into a 60% reduction in the risk of disease progression or death (HR[95%CI]: 0.40[0.28-0.57], p< 0.000001). At twelve months, 51.7% of patients in the Glofit-GemOx arm were alive and free of progression (vs. 25.2% in the R-GemOx arm). The CR rate was statistically significant at primary analysis, with an increased difference between treatment arms in the updated analysis (58.5% vs. 25.3%, 33.2% difference, p< 0.0001).

Median number of cycles received was higher with Glofit-GemOx vs. R-GemOx (11 vs. 4). Adverse event (AE) rates were higher with Glofit-GemOx vs. R-GemOx, including Grade 3–5 AEs (77.8 vs. 40.9%), and serious AEs (54.4 vs. 17.0%). In patients exposed to glofitamab, cytokine release syndrome (CRS) was reported in 44.2% of patients, of which most were grade 1 (31.4%) or grade 2 (10.5%). Events consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in four patients (2.3%).

Conclusion

Fixed duration glofitamab added to GemOx demonstrated a statistically significant and clinically meaningful OS benefit in patients with R/R DLBCL, who were ineligible for ASCT. Glofit-GemOx was tolerable, with AEs that were consistent with the known risks of the study drugs. As such, glofitamab is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomised phase III trial and these results support the use of Glofit-GemOx for the treatment of R/R DLBCL.

Reference

Abramson J, et al. Glofitamab plus Gemcitabine and Oxaliplatin (Glofit-GemOx) for Relapsed/Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL): Results of a Global Randomized Phase III Trial (STARGLO). Presented at EHA 2024; Abstract LB3438.